The overall objective of this project is to determine if retinoids will reverse the transplacental carcinogenic effect of N-ethyl-N-nitrosourea in rats. Essentially all of the offspring of pregnant females treated with a proper dose of this agent develop cancer of the cental nervous system. We propose to administer, to pregnant Sprague-Dawley rats, a dose (10 mg/kg) expected to induce an 80% incidence of malignant tumors of the central nervous system in the offspring. Since the tumors do not appear for several weeks, we will have sufficient time to test retinoids as agents to prevent their occurrence. Retinyl acetate, 13-cis-retinoic acid, and all-trans-retinoic acid will be administered at two different, nontoxic dose levels, starting when the offspring are 4 weeks old and continuing for their lifetime. Retinyl acetate is known to be effective in preventing mammary cancer induced by carcinogens. All-trans- and 13-cis-retinoic acid are effective in preventing carcinogen-induced bladder cancer. The different dose levels will allow us to determine if a dose-response relationship exists. At designated times during the study, retinoid levels in tissues of some of the animals in each group will be determined by colorimetric procedures and by high-pressure liquid chromatography; and the liver will be examined for evidence of toxicity. These determinations will assure that adequate, nontoxic doses of retinoids are being administered. Also, some of the animals of each group will be sacrificed so that the number of thymidine incorporating foci in the brains can be determined. The progression of these foci, which are thought to represent preneoplastic lesions, can be followed in control rats and rats treated with retinoids. The incidence and number of neurogenic tumors per rat will be evaluated for each group of rats by a necropsy procedure that involves examination of all major tissues and histological evaluation of all gross lesions. Procedures for the safe handling of carcinogens will be applied. If retinoids prove to be effective in preventing neurologic malignancies, humans exposed to carcinogens causing such cancer could be given retinoids as a measure to prevent development of the disease.